1. Field of the Invention
The present invention relates to a novel strain of an animal. The present animal is an experimental mouse, which is suffering or will suffer from alopecia, has a small number of hair follicles, and has a deposition of melanin pigment in the epidermal basal layer and in the corium connective tissue. These phenotypes are inherited by an autosomal dominant gene. Due to these characteristics, the present mouse is very useful in the field of dermatology, especially as an animal model for human disease or an experimental animal in studies of alopecia, photodermatosis, and further, as an experimental animal for studies of transdermal absorption in the drug metabolism field. Accordingly, the present invention is useful in the medical field, including pharmacology, for studies of the pathogenesis and therapy of human alopecia and photodermatosis, and for studies of transdermal drug absorption.
2. Description of the Related Art
As mice exhibiting hereditary hypotrichosis, atrichosis or alopecia in the entire hair covering thereof, there are known hairless (H. C. Brooke. Hairless mice. J. Hered. 17,173-174 (1926.); rhino (A. Howard. "Rhino", an allele of hairless in the house mouse. J. Hered. 31, 467-470 (1940).); ichthyosis (T. C. Cater and R. S. Phillips. Ichthyosis, a new recessive mutant in the house mouse. J.Hered. 41, 297-300 (1950).); bald (E. D. Garber. "Bald", a second allele of hairless in the house mouse. J. Hered. 43, 45-46 (1952).); ragged (T. C. Cater and R. J. S. Phillips. Ragged, a semidominant coat texture mutant. J. Hered. 45, 151-154 (1954).); asebia (A. H. Gates and M. Karasek. Hereditary absence of sebaceous glands in the mouse, Science 148, 1471-1473 (1965).); nude (S. P. Flanagan. `Nude`, a new hairless gene with pleiotropic effects on the mouse. Genet. Res., Camb. 8, 295-309 (1966).); naked (H. Muto, developmental changes of epidermal cells of naked mouse, Igaku to Seibutsugaku (Medicine and Biology) 75, 28-31 (1967).); and glabrous (S. Tsujii and H. Matsushita. "Glabrous" a new hair deficient mutant in the house mouse. Jpn. J. Genetics 47, 297-299(1972).) Almost all of the above, however, are governed by a recessive inheritance, and therefore, are basically different from the present mouse.
Only the naked mouse is reported to be governed by a dominant gene, but this mouse is clearly different from the present mouse in that the reported naked mouse can be distinguished from a normal individual at 10 weeks old, a cornification of the skin in the naked mouse is remarkable, and this cornification causes alopecia. Known mice having alopecia are listed in Table 1.
TABLE 1 __________________________________________________________________________ List of reports on mice exhibiting hereditary hypotrichosis, atrichosis, hairless or alopecia No. 1 Genetic type Name (gene) Type of alopecia, and characteristics of hair and Other characteristics Author __________________________________________________________________________ hairless Recessive When about six weeks old, grew a short coat, Bad in Nursing and vibrissae is Brooke (hr) as if it had been singed, which disappeared in a few normal (1926) rhino Recessive Epilation occurs from 2 weeks old, entire epilation Elongation of the claws Howard (hr.sup.rh) except for vibrissae from about 50 days old. The skin reduced mammary gland (1940). remarkable wrinkles as time elapses, a large number of cysts are formed. No cyclic regrowth of tylotrichs. ichthyosis Recessive (ic) The skin dries hardens and becomes scaly. Dosal guard Vibrissae are short and Cater et al. are still scarcely visible at 6 days old. An older mouse often curled. (1950) grows a thin, curly coat. bald Recessive Hairs were normal in appearance until the 16th day when Vibrissae are lost after Garben (ba) hair just above the eyes and around the nose started to fall out, 30 days but shorter, (1952) and usually completely bald within 22-28 days. vibrissae may sometimes appear after several weeks. ragged Semidominant Homo: The ears and fail are pigmented. Cater et al. (Ra) Adults are naked, their few isolated pelage hairs being confined Most of homozygotes die shortly. (1953) to the posterior and ventral part of the body. Sinus The distribution of the yellow are few and short. agouti pattern is abnormal. Hetero: Distinguished from normal individuals by 9 days old. The coat of adult looks sparse and lacks cohesion. Many guard hairs are present. Proportion of zigzags is much lower than in normal mice. asebia Recessive Distinguished from normal individuals when 7-9 days Delay of growth. Cates et al. (ab) Alopecia increase until adulthood. Lack of sebaceous (1965) The base of follicle sometimes exhibits excessive development, but hair production is faulty. Pruritus (inflammation with itching) occurs around eyes in old-age. Hyperkeratosis. nude Recessive Growth of a first coat is inhibited. Flanagan (nu) (1966) naked Dominant Distinguished from normal individuals on the day 10 after bith Muto (N) (because of poor hair in parts other than lumbar and (1972) Hyperkeratosis of skin is remarkable, and epilation caused thereby. Hair root cells are relatively normal. glabrous Recessive Failure of a normal juvenile hair growth. Abnormalities Twisted and crooked Tsujii et al. (gs) for development are readily detectable by the fifth of Complete absence of (1972)ous day after birth, Hyperkeratosis. Monotrich, zigzag is glands. Smaller in size than present. their normal litter mates at birth. __________________________________________________________________________
Most mice reported to exhibit a hypotrichosis an atrichosis, an alopecia or a hairless, in hereditary, are epilated soon after birth, the epilation rapidly progresses, the cornification of the skin is accelerated, and a remarkable number of wrinkles is formed.
Although as an animal model for alopecia and photodermatosis of human, mice not exhibiting an extreme hypertrophy of the skin and not accelerating cornification are preferred but mice satisfying these requirements have not been found. Moreover, since a mouse does not have melanocyte in the epidermis and has many hair follicles, it is not suitable as an animal model for a human for experiments of an induction of photodermatosis or for transdermal absorption experiments.
Although mice are widely used as the most useful experimental animals in the medical and pharmacological research fields, and many animal models for human diseases have been developed, in the field of alopecia, a mouse model acceptable for practical use has not yet been developed.
Therefore, the present invention is intended to provide a decalvant mouse suitable as an alopecia model for a human and not having the above-mentioned drawbacks. To obtain suitable model animals, the present inventors found a mutant mouse and carried out a breeding and tests of characteristics, and as a result, succeeded in the breeding of a novel strain of mouse.